Emil F. Pai
Diploma, University of Heidelberg, 1976
Dr rer nat, University of Heidelberg, 1978
Postdoc, Max-Planck-Institute for Medical Research, 1978-1980
Visiting Scientist, University of California at Santa Barbara, 1982-1983
|Address||MSB, Room 5358
1 KIng's College Circle
Toronto, ON M5S 1A8
Emil F. Pai was born and raised in Heidelberg, Germany. After undergraduate studies in Chemistry at Heidelberg University, he moved to the Department of Biophysics at the Max-Planck-Institute for Medical Research for training in biochemistry and macromolecular crystallography. He identified the substrate binding sites of adenylate kinase and determined the first crystal structure of a flavoenzyme, glutathione reductase. After receiving his doctoral degree, he stayed on at the MPI, first as Postdoc then as Group Leader. From 1982-83 he worked in T.C. Bruice’s lab at the University of California at Santa Barbara on heme models of cytochrome P-450 oxidations. Back at the MPI, he contributed to the crystal structure of the muscle protein actin and determined the three-dimensional fold of the first oncoprotein, H-ras p21. In 1991, he came to the Biochemistry Department as the NSERC Industrial Research Chair in Protein Crystallography. He has over 200 publications to his name.
In the News
The present members of the Pai lab (Natasha Kruglyak, Ondrej Halgas, and Pedram Mehrabi) are interested in the way structure of proteins determines their function. Specific proteins of interest are the bacterial Mg channel CorA, enzymes that break C-F bonds, antibodies that trap misfolded forms of prion proteins, an anti-HIV-1 antibody, and the evolution and maturation of IgG molecules. They have access to several in-house and synchrotron X-ray sources as well as automated crystallization equipment. A newly developing focus deals with time-resolved crystallography and electron diffraction. All the projects involve close collaborations with international, Canadian, and Toronto laboratories.
The structural determinants of protein function
Knowledge of the three-dimensional structure of a given protein is an absolutely essential prerequisite for fully understanding the chemical basis of a catalytic mechanism of an enzyme or for interpreting the way antibodies evolve and interact with their targets. The Pai lab uses biochemical and molecular biology techniques together with X-ray crystallography and computational methods to establish the molecular architecture of proteins. The research focus of the lab is rather broad and includes the following projects:
Molecular transport and homeostasis of Mg-ions
Dehalogenase enzymes able to break C-F bonds
Structural basis of antibody maturation and their effect on antigen recognition
Structures of early intermediates in prion protein misfolding
All members of the lab are eager to integrate their results with biochemical and molecular-biological data, either collected in-house or available through local, national or international collaborations with experts in the field.
How Mg-ions cross cell membranes
The lab determined the crystal structure of the first Mg-ion channel, a homopentameric membrane protein. It also generated about 80 mutants of the protein designed to probe the still elusive mechanism of ion transport through the 50 Å long central tube. The ongoing investigation of its transport and regulation mechanisms applies a broad selection of biochemical and biophysical techniques, including collaborations in EPR spectroscopy (O. Ernst), electrophysiology (C. Bear) and computational biology (R. Pomes).
How to break C-F bonds
The lab studies several enzymes capable of removing halogen atoms from organic compounds. These enzymes were identified from the genomes of a wide array of microorganisms by bioinformatics means and confirmed by activity screens (with E. Edwards). Most remarkably, this collection includes a number of proteins that are able to break covalent C-F bonds, the most stable bonds in organic chemistry. The lab determined the crystal structures of several of these dehalogenases, described substrate/inhibitor/product complexes before moving into the field of time-resolved crystallography and electron diffraction (K. Moffat, U Chicago, D. Miller, MPI Hamburg).
To read our newest paper in Science identifying entropic balancing between the dimers of the enzyme fluoroacetate dehalogenase from Rhodopseudomonas palustris click on the following links:
An artistic interpretation of the enzyme fluoroacetate dehalogenase binding substrate (green) in the left subunit and releasing bound water molecules (red) in the right-hand subunit.
Structures of early misfolding intermediates of prion proteins
The lab uses Fab-fragments of antibodies that specifically recognize misfolded forms of prion protein and SOD1 to trap intermediates of the misfolding transition. Starting with Fab-epitope peptide complexes, the goal is to sufficiently stabilize intermediates of full length proteins to allow crystallization and structural characterization.
Awards & Distinctions
1981 — Otto-Hahn-Medal, Max-Planck-Society
1991-2001 — NSERC Industrial Research Chair in Protein Crystallography
1999 — Premier's Research Excellence Award
2002-2015 — Canada Research Chair (tier I) in Structural Biology
2010 — Canadian Who's Who
View all publications on PubMed
Substrate distortion contributes to the catalysis of orotidine-5’-monophosphate decarboxylase.
Fujihashi M, Ishida T, Juroda S, Kotra LP, Pai EF, Miki K.
J Amer Chem Soc. 2013 135:17432-43. Read
Structures and regulation of magnesium selective ion channels.
Payandeh J, Pfoh R, Pai EF.
Biochim Biophys Acta - Biomembranes 2013 1828:2778-92. Read
N-terminal helix-cap in alpha-helix 2 modulates beta-state misfolding in rabbit and hamster prion protein.
Sweeting B, Brown E, Khan MQ, Chakrabartty A, Pai EF.
PLoS ONE 2013 8:e63047 Read
Structural asymmetry in the magnesium channel CorA points to sequential allosteric regulation.
Pfoh R, Li A, Chakrabarti N, Payandeh J, Pomes R, Pai EF.
Proc Natl Acad Sci USA 2012 109:18809-14. Read
Protein conformational gating of enzymatic activity in xanthine oxidoreductase.
Ishikita H, Eger BT, Okamoto K, Nishino T, Pai EF.
J Amer Chem Soc 2012 134:999-1009. Read
Crystal structure of the passenger domain of the Escherichia coli autotransporter EspP.
Khan S, Mian HS, Sandercock LE, Chrigadze NY, Pai EF.
J Mol Biol 2011 413:985-1000. Read
Mapping the reaction coordinates of enzymatic defluorination.
Chan WY, Yakunin AF, Edwards EA, Pai EF.
J Amer Chem Soc 2011 133:7461-8. Read
Crystal structure of metarhodopsin II.
Choe HW, Kim YJ, Park JH, Morizumi T, Pai EF, Krauß N, Hofmann KP, Scheerer P, Ernst O.
Nature (London) 2011 471:651-5. Read
The role of dimer asymmetry and protomer dynamics in enzyme catalysis.
Kim TH, Mehrabi P, Ren Z, Sljoka A, Ing C, Bezginov A, Ye L, Pomes R, Prosser RS, Pai EF.
Science 2017 355:262, eaag2355 Read